β-Thalassemia (β-thal) is one of the most common monogenic recessive inherited diseases worldwide. The mutation spectrum of β-thal has been increasingly broadened by various genetic testing methods. The discovery and identification of novel and rare pathogenic thalassemia variants enable better disease prevention, especially in high prevalence regions. In this study, a Chinese thalassemia family with an unclear etiology was recruited to the Thalassemia Screening Program. Blood samples collected from them were primarily screened by hematology analysis and clinical routine genetic screening. Subsequently, targeted next-generation sequencing (NGS) and Sanger sequencing were performed to find and identify a novel deletion variant. The deletion, discovered by targeted NGS, was validated through real-time quantitative polymerase chain reaction (qPCR). First, a large novel β-thal deletion (3488 bp) related to a high Hb F level, NC_000011.9: g.5245533_5249020del (Chongqing deletion) (GRCh37/hg19), was found and identified in the proband and her mother. The deletion removed the entire β-globin gene and led to absent β-globin (β0). We then validated this large novel deletion in the proband and her mother by qPCR. We first discovered and identified a large novel β-thal deletion related to elevated Hb F level, it helps broaden the spectrum of pathogenic mutants that may cause β-thal intermedia (β-TI) or β-thal major (β-TM), paving the way for effective thalassemia screening. Next-generation sequencing has the potential of finding rare and novel thalassemia mutants.
{"title":"Targeted Next-Generation Sequencing Reveals a Large Novel β-Thalassemia Deletion that Removes the Entire <i>HBB</i> Gene.","authors":"Zhen-Zhen Yin, Jian Yao, Feng-Xiang Wei, Chu-Yan Chen, Hong-Mei Yan, Ming Zhang","doi":"10.1080/03630269.2022.2145964","DOIUrl":"https://doi.org/10.1080/03630269.2022.2145964","url":null,"abstract":"<p><p>β-Thalassemia (β-thal) is one of the most common monogenic recessive inherited diseases worldwide. The mutation spectrum of β-thal has been increasingly broadened by various genetic testing methods. The discovery and identification of novel and rare pathogenic thalassemia variants enable better disease prevention, especially in high prevalence regions. In this study, a Chinese thalassemia family with an unclear etiology was recruited to the Thalassemia Screening Program. Blood samples collected from them were primarily screened by hematology analysis and clinical routine genetic screening. Subsequently, targeted next-generation sequencing (NGS) and Sanger sequencing were performed to find and identify a novel deletion variant. The deletion, discovered by targeted NGS, was validated through real-time quantitative polymerase chain reaction (qPCR). First, a large novel β-thal deletion (3488 bp) related to a high Hb F level, NC_000011.9: g.5245533_5249020del (Chongqing deletion) (GRCh37/hg19), was found and identified in the proband and her mother. The deletion removed the entire β-globin gene and led to absent β-globin (β<sup>0</sup>). We then validated this large novel deletion in the proband and her mother by qPCR. We first discovered and identified a large novel β-thal deletion related to elevated Hb F level, it helps broaden the spectrum of pathogenic mutants that may cause β-thal intermedia (β-TI) or β-thal major (β-TM), paving the way for effective thalassemia screening. Next-generation sequencing has the potential of finding rare and novel thalassemia mutants.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10439499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-01DOI: 10.1080/03630269.2022.2122497
Sona B Nair, Arundhati S Athalye, Madhavi Panphalia, Firuza R Parikh
Coinheritance of a high oxygen affinity structural hemoglobin (Hb) variant along with a thrombophilia marker is a rare occurrence. This may lead to a multi fold increase in the risk of thrombosis in patients. We report here a first case of Hb Coombe Park (HBA2: c.382A>G; p.Lys128Glu) from India, coinherited with a novel mutation (c.839C>G; p.Ser280Ter) on the SERPINC1 gene. This coinheritance has not been reported before. Though the patient is presently asymptomatic, identification of these variants will help in genetic counseling and to decide the future course of action in case of any clinical complications.
高氧亲和性结构血红蛋白(Hb)变异与血栓形成标志物的共遗传是罕见的。这可能导致患者血栓形成风险增加数倍。我们在此报告首例Hb Coombe Park (HBA2: c.382A>G;p.Lys128Glu)来自印度,共遗传了一个新的突变(c.839C>G;p.Ser280Ter)在serinc1基因上。这种共遗传在以前没有报道过。虽然患者目前无症状,但这些变异的识别将有助于进行遗传咨询,并在出现任何临床并发症时决定未来的行动方案。
{"title":"First Report of an α Chain Variant [Hb Coombe Park (<i>HBA2</i>: c.382A>G)] from India, Coinherited with a Novel <i>SERPINC1</i> Gene Mutation: A Double Whammy?","authors":"Sona B Nair, Arundhati S Athalye, Madhavi Panphalia, Firuza R Parikh","doi":"10.1080/03630269.2022.2122497","DOIUrl":"https://doi.org/10.1080/03630269.2022.2122497","url":null,"abstract":"<p><p>Coinheritance of a high oxygen affinity structural hemoglobin (Hb) variant along with a thrombophilia marker is a rare occurrence. This may lead to a multi fold increase in the risk of thrombosis in patients. We report here a first case of Hb Coombe Park (<i>HBA2</i>: c.382A>G; p.Lys128Glu) from India, coinherited with a novel mutation (c.839C>G; p.Ser280Ter) on the <i>SERPINC1</i> gene. This coinheritance has not been reported before. Though the patient is presently asymptomatic, identification of these variants will help in genetic counseling and to decide the future course of action in case of any clinical complications.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10827822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-01DOI: 10.1080/03630269.2022.2142607
Hibah A Almasmoum, Aisha Tabassum, Mohammad Shahid Iqbal, Refal Abo-Alshamat, Waad Aqeeli
The National Premarital Screening Program, which includes sickle cell disease and thalassemia, was made mandatory in 2004 by the Kingdom of Saudi Arabia (KSA), and the earlier studies have shown a poor knowledge and negative attitude toward this program in the different study groups. This study was conducted to assess the knowledge and attitudes toward premarital screening (PMS) in a randomly selected national sample of the Saudi population, 18 years and above. This was a cross-sectional study conducted in the Saudi population in the western region between July and December 2021. Valid and reliable questionnaire and data were collected from 893 participants aged ≥18 years. The χ2 test was used to ascertain if there is an association between categorical variables. Multivariate logistic regression was used to determine factors predicting satisfactory knowledge. All 893 study participants had heard about PMS with 625 (70.0%), 244 (27.3%) and 24 (2.7%) having satisfactory, fair and poor knowledge, respectively. Participants aged 26-35 years (p =0 .038), females (p < 0.001), those with higher education (p = 0.003) and employed (p = 0.004), had a better knowledge compared to other groups. Most of the participants had a positive attitude toward PMS. There is a changing trend in the knowledge and attitude toward PMS with a greater number of people wanting to go for PMS. There is also an improvement in the number of participants opting out of marriage in case of incompatibility with their future partner. However, the health education programs need to be improved regarding the hemoglobinopathies.
{"title":"Knowledge and Attitude toward Hemoglobinopathies in Premarital Screening Program among the General Population in the Western Region of Saudi Arabia.","authors":"Hibah A Almasmoum, Aisha Tabassum, Mohammad Shahid Iqbal, Refal Abo-Alshamat, Waad Aqeeli","doi":"10.1080/03630269.2022.2142607","DOIUrl":"https://doi.org/10.1080/03630269.2022.2142607","url":null,"abstract":"<p><p>The National Premarital Screening Program, which includes sickle cell disease and thalassemia, was made mandatory in 2004 by the Kingdom of Saudi Arabia (KSA), and the earlier studies have shown a poor knowledge and negative attitude toward this program in the different study groups. This study was conducted to assess the knowledge and attitudes toward premarital screening (PMS) in a randomly selected national sample of the Saudi population, 18 years and above. This was a cross-sectional study conducted in the Saudi population in the western region between July and December 2021. Valid and reliable questionnaire and data were collected from 893 participants aged ≥18 years. The χ<sup>2</sup> test was used to ascertain if there is an association between categorical variables. Multivariate logistic regression was used to determine factors predicting satisfactory knowledge. All 893 study participants had heard about PMS with 625 (70.0%), 244 (27.3%) and 24 (2.7%) having satisfactory, fair and poor knowledge, respectively. Participants aged 26-35 years (<i>p</i> =0<i> .</i>038), females (<i>p</i> < 0.001), those with higher education (<i>p</i> = 0.003) and employed (<i>p</i> = 0.004), had a better knowledge compared to other groups. Most of the participants had a positive attitude toward PMS. There is a changing trend in the knowledge and attitude toward PMS with a greater number of people wanting to go for PMS. There is also an improvement in the number of participants opting out of marriage in case of incompatibility with their future partner. However, the health education programs need to be improved regarding the hemoglobinopathies.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10425450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-01DOI: 10.1080/03630269.2022.2121215
Abbey Renner, Mitchell Love, Elizabeth Garrett, Alexander Douglas, Micah Kee, Benjamin Heigle, Audrey Wise, Ryan Ottwell, Micah Hartwell, Matt Vassar
Sickle cell disease significantly impacts one's quality of life (QOL); thus, randomized controlled trials (RCTs) have integrated patient-reported outcomes (PROs) to assess patients' health from their perspective. We aim to evaluate the completeness of reporting of PROs included in sickle cell disease RCTs. We searched MEDLINE, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) for published sickle cell disease RCTs with at least one PRO measure from 2006 to 2021. In a masked, duplicate fashion, two investigators evaluated RCTs using the Consolidated Standards of Reporting in Trials (CONSORT)-PRO adaptation and Cochrane Collaboration Risk of Bias (RoB) 2.0 tool. The primary objective was mean percent completeness of the CONSORT-PRO adaptation. Additional relationships between trial characteristics and completeness of reporting were evaluated. Mean completeness of reporting of RCTs was 41.49% (SD = 20.90). Randomized controlled trials with primary outcomes were more complete (57.50%, SD = 8.33) than RCTs with secondary PROs (33.48%, SD = 20.91). We did not find a significant difference in completion between trials with primary PROs and secondary PROs (t1 = 2.07; p = 0.06). Our secondary objectives included factors that may be associated with completeness of PRO reporting. Of the 12 included studies, five were considered to be overall 'high' RoB (41.67%). In each of the five domains, the majority of studies received 'low' RoB evaluations. Incomplete PRO reporting was common within sickle cell RCTs. Therefore, we recommend future RCTs including PROs should take measures to increase completeness of reporting.
{"title":"Sickle Cell Disease and Quality of Life: An Evaluation of Reporting of Patient-Reported Outcomes in Randomized Controlled Trials.","authors":"Abbey Renner, Mitchell Love, Elizabeth Garrett, Alexander Douglas, Micah Kee, Benjamin Heigle, Audrey Wise, Ryan Ottwell, Micah Hartwell, Matt Vassar","doi":"10.1080/03630269.2022.2121215","DOIUrl":"https://doi.org/10.1080/03630269.2022.2121215","url":null,"abstract":"<p><p>Sickle cell disease significantly impacts one's quality of life (QOL); thus, randomized controlled trials (RCTs) have integrated patient-reported outcomes (PROs) to assess patients' health from their perspective. We aim to evaluate the completeness of reporting of PROs included in sickle cell disease RCTs. We searched MEDLINE, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) for published sickle cell disease RCTs with at least one PRO measure from 2006 to 2021. In a masked, duplicate fashion, two investigators evaluated RCTs using the Consolidated Standards of Reporting in Trials (CONSORT)-PRO adaptation and Cochrane Collaboration Risk of Bias (RoB) 2.0 tool. The primary objective was mean percent completeness of the CONSORT-PRO adaptation. Additional relationships between trial characteristics and completeness of reporting were evaluated. Mean completeness of reporting of RCTs was 41.49% (SD = 20.90). Randomized controlled trials with primary outcomes were more complete (57.50%, SD = 8.33) than RCTs with secondary PROs (33.48%, SD = 20.91). We did not find a significant difference in completion between trials with primary PROs and secondary PROs (t<sub>1</sub> = 2.07; <i>p</i> = 0.06). Our secondary objectives included factors that may be associated with completeness of PRO reporting. Of the 12 included studies, five were considered to be overall 'high' RoB (41.67%). In each of the five domains, the majority of studies received 'low' RoB evaluations. Incomplete PRO reporting was common within sickle cell RCTs. Therefore, we recommend future RCTs including PROs should take measures to increase completeness of reporting.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10439456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-01DOI: 10.1080/03630269.2022.2138429
Ke Wang, Ting Yi, Wen-Tao Wu, Juan Lu, Li-Na He, Hong-Ping Zhou, Jiang-Wei Ke, Fa-Di Liu
Thalassemia is one of southern China's most common inherited disorders. Little is known about the genotypes of thalassemia in children in Jiangxi Province, the People's Republic of China (PRC). Two thousand, nine hundred and fifty-two children with suspected thalassemia were recruited from August 2016 to December 2020 at the Jiangxi Provincial Children's Hospital, Nanchang, PRC. Reverse dot-blot hybridization was used to detect α- and β-thalassemia (α- and β-thal) genotypes. A rare mutation was detected using gap-polymerase chain reaction (gap-PCR) and gene sequencing. The overall distribution of thalassemia (1534 cases) was 51.96%, and the detection rate of α-thal (616 cases), β-thal (888 cases) and concurrent α- and β-thalassemias (30 cases) was 20.86, 30.08, and 1.02%, respectively. A rare α-thal genotype, -α27.6/- -SEA (Southeast Asian), was identified. Seventy-eight cases of severe β-thal were detected, accounting for 8.78% of the cases, including 56 double heterozygous cases and 22 cases that were homozygous. Both α- and β-thalassemias are widely distributed in the children of Jiangxi Province. Thalassemia genetic testing is essential to establish a comprehensive thalassemia prevention program and improve public education.
{"title":"Investigation of the Distribution of Thalassemia in Children in Jiangxi Province, the People's Republic of China.","authors":"Ke Wang, Ting Yi, Wen-Tao Wu, Juan Lu, Li-Na He, Hong-Ping Zhou, Jiang-Wei Ke, Fa-Di Liu","doi":"10.1080/03630269.2022.2138429","DOIUrl":"https://doi.org/10.1080/03630269.2022.2138429","url":null,"abstract":"<p><p>Thalassemia is one of southern China's most common inherited disorders. Little is known about the genotypes of thalassemia in children in Jiangxi Province, the People's Republic of China (PRC). Two thousand, nine hundred and fifty-two children with suspected thalassemia were recruited from August 2016 to December 2020 at the Jiangxi Provincial Children's Hospital, Nanchang, PRC. Reverse dot-blot hybridization was used to detect α- and β-thalassemia (α- and β-thal) genotypes. A rare mutation was detected using gap-polymerase chain reaction (gap-PCR) and gene sequencing. The overall distribution of thalassemia (1534 cases) was 51.96%, and the detection rate of α-thal (616 cases), β-thal (888 cases) and concurrent α- and β-thalassemias (30 cases) was 20.86, 30.08, and 1.02%, respectively. A rare α-thal genotype, -α<sup>27.6</sup>/- -<sup>SEA</sup> (Southeast Asian), was identified. Seventy-eight cases of severe β-thal were detected, accounting for 8.78% of the cases, including 56 double heterozygous cases and 22 cases that were homozygous. Both α- and β-thalassemias are widely distributed in the children of Jiangxi Province. Thalassemia genetic testing is essential to establish a comprehensive thalassemia prevention program and improve public education.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10492371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-01DOI: 10.1080/03630269.2022.2142608
Nishith A Vachhani, Daya J Vekariya, Roshan B Colah, Heena N Kashiyani, Sanjeev L Nandani
Hemoglobinopathies are common genetic disorders of the hemoglobin (Hb) molecule. Globally, 7.0% of the population are carriers of thalassemia with 300,000-400,000 affected births each year. There are >40 million carriers of β-thalassemia (β-thal) in India with 10,000-12,000 affected births every year. This makes control programs crucial in this vast and diverse country. The present study was undertaken to find out the burden of hemoglobinopathies, and in particular, the prevalence of β-thal carriers in the population of Saurashtra region of Gujarat in Western India. A total of 16,780 individuals, including school and college students, were screened. Complete blood counts (CBCs) and high performance liquid chromatography (HPLC) analysis were performed. We detected 1891 (11.26%) individuals with different hemoglobinopathies, of whom 758 (4.52%) were diagnosed to carry β-thal trait, 104 (0.62%) carried Hb D-Punjab (HBB: c.364G>C) trait, 61 (0.36%) carried sickle cell trait, 32 (0.19%) carried δβ-thal trait/HPFH (hereditary persistence of fetal Hb) trait, and other hemoglobinopathies were identified in smaller numbers (0.15%). We encountered 27 individuals with mean corpuscular Hb (MCH) <27.0 pg and mean corpuscular volume (MCV) <80.0 fL levels, who had borderline Hb A2 levels (3.2-3.5%). Twenty castes showed the presence of β-thal or other hemoglobinopathies. A high prevalence of β-thal was found in the Sindhis (11.67%), Lohanas (9.71%), Brahmins (6.31%), Bharvads (6.94%), Harijans (7.57%) and Vankars (7.77%). All the heterozygotes were given appropriate counseling. A multi pronged approach, including screening of high school and college students, needs to be considered for this vast and ethnically diverse country to reduce the burden of hemoglobinopathies.
血红蛋白病是血红蛋白(Hb)分子常见的遗传性疾病。在全球范围内,7.0%的人口是地中海贫血携带者,每年有30万至40万新生儿受影响。印度有超过4000万β-地中海贫血(β-thal)携带者,每年有10,000-12,000名受影响的新生儿。这使得控制项目在这个幅员辽阔、多样化的国家至关重要。本研究旨在了解印度西部古吉拉特邦绍拉什特拉地区人群中血红蛋白病的负担,特别是β-thal携带者的患病率。共有16,780人接受了筛查,其中包括在校学生和大学生。全血细胞计数(CBCs)和高效液相色谱(HPLC)分析。我们检测到1891例(11.26%)不同血红蛋白病个体,其中758例(4.52%)携带β-thal性状,104例(0.62%)携带Hb D-Punjab (HBB: C . 364g >C)性状,61例(0.36%)携带镰状细胞性状,32例(0.19%)携带δβ-thal性状/HPFH(胎儿Hb遗传持续性)性状,其他血红蛋白病较少(0.15%)。我们遇到了27例平均红细胞Hb (MCH) 2水平(3.2-3.5%)的患者。20个种姓出现β-thal或其他血红蛋白病。β-thal在信德族(11.67%)、洛哈纳族(9.71%)、婆罗门族(6.31%)、巴瓦德族(6.94%)、哈里贾族(7.57%)和万卡尔族(7.77%)中患病率较高。对所有杂合子给予适当的辅导。在这个幅员辽阔、种族多样的国家,需要考虑采取多管齐下的方法,包括对高中生和大学生进行筛查,以减轻血红蛋白病的负担。
{"title":"Spectrum of β-Thalassemia and Other Hemoglobinopathies in the Saurashtra Region of Gujarat, India: Analysis of a Large Population Screening Program.","authors":"Nishith A Vachhani, Daya J Vekariya, Roshan B Colah, Heena N Kashiyani, Sanjeev L Nandani","doi":"10.1080/03630269.2022.2142608","DOIUrl":"https://doi.org/10.1080/03630269.2022.2142608","url":null,"abstract":"<p><p>Hemoglobinopathies are common genetic disorders of the hemoglobin (Hb) molecule. Globally, 7.0% of the population are carriers of thalassemia with 300,000-400,000 affected births each year. There are >40 million carriers of β-thalassemia (β-thal) in India with 10,000-12,000 affected births every year. This makes control programs crucial in this vast and diverse country. The present study was undertaken to find out the burden of hemoglobinopathies, and in particular, the prevalence of β-thal carriers in the population of Saurashtra region of Gujarat in Western India. A total of 16,780 individuals, including school and college students, were screened. Complete blood counts (CBCs) and high performance liquid chromatography (HPLC) analysis were performed. We detected 1891 (11.26%) individuals with different hemoglobinopathies, of whom 758 (4.52%) were diagnosed to carry β-thal trait, 104 (0.62%) carried Hb D-Punjab (<i>HBB</i>: c.364G>C) trait, 61 (0.36%) carried sickle cell trait, 32 (0.19%) carried δβ-thal trait/HPFH (hereditary persistence of fetal Hb) trait, and other hemoglobinopathies were identified in smaller numbers (0.15%). We encountered 27 individuals with mean corpuscular Hb (MCH) <27.0 pg and mean corpuscular volume (MCV) <80.0 fL levels, who had borderline Hb A<sub>2</sub> levels (3.2-3.5%). Twenty castes showed the presence of β-thal or other hemoglobinopathies. A high prevalence of β-thal was found in the Sindhis (11.67%), Lohanas (9.71%), Brahmins (6.31%), Bharvads (6.94%), Harijans (7.57%) and Vankars (7.77%). All the heterozygotes were given appropriate counseling. A multi pronged approach, including screening of high school and college students, needs to be considered for this vast and ethnically diverse country to reduce the burden of hemoglobinopathies.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10434081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-07-01Epub Date: 2022-09-15DOI: 10.1080/03630269.2022.2118605
Lara Calcagno, Maria M Ciriello, Monica Maccarini, Massimo Mogni, Massimo Maffei, Giuseppina Barberio, Sauro Maoggi, Domenico Coviello, Giovanni Ivaldi
We report a novel mutation on the β-globin gene in a 68-year-old woman of Sicilian origin living in Alessandria, Italy. This mutation produces a hemoglobin (Hb) variant of Hb A that was detected by the capillary electrophoresis (CE) method during measurement of Hb A1c. The variant Hb did not separate from Hb A using different high performance liquid chromatography (HPLC) instruments. Direct DNA sequencing revealed a G>T transversion at codon 37 and subsequent substitution of a tryptophan residue for a leucine residue. The new Hb variant was named Hb Alessandria [β37(C3)Trp→Leu; HBB: c.113G>T]. The p50 value was slightly decreased while the stability test at 37 °C in isopropyl alcohol and the main erythrocyte parameters were normal. Overall, the patient appeared clinically normal.
{"title":"Hb Alessandria [β37(C3)Trp→Leu; <i>HBB</i>: c.113G>T]: a Novel Variant on the <b>β</b>-Globin Chain with Slightly Increased Affinity for Oxygen Detected by Capillary Electrophoresis.","authors":"Lara Calcagno, Maria M Ciriello, Monica Maccarini, Massimo Mogni, Massimo Maffei, Giuseppina Barberio, Sauro Maoggi, Domenico Coviello, Giovanni Ivaldi","doi":"10.1080/03630269.2022.2118605","DOIUrl":"https://doi.org/10.1080/03630269.2022.2118605","url":null,"abstract":"<p><p>We report a novel mutation on the β-globin gene in a 68-year-old woman of Sicilian origin living in Alessandria, Italy. This mutation produces a hemoglobin (Hb) variant of Hb A that was detected by the capillary electrophoresis (CE) method during measurement of Hb A<sub>1c</sub>. The variant Hb did not separate from Hb A using different high performance liquid chromatography (HPLC) instruments. Direct DNA sequencing revealed a G>T transversion at codon 37 and subsequent substitution of a tryptophan residue for a leucine residue. The new Hb variant was named Hb Alessandria [β37(C3)Trp→Leu; <i>HBB</i>: c.113G>T]. The p50 value was slightly decreased while the stability test at 37 °C in isopropyl alcohol and the main erythrocyte parameters were normal. Overall, the patient appeared clinically normal.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40358924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-07-01DOI: 10.1080/03630269.2022.2072320
Margaret Locke, Paavani S Reddy, Sherif M Badawy
Iron chelation therapy (ICT) is essential to prevent complications of iron overload in patients with transfusion-dependent thalassemia. However, the role that adherence to ICT plays in health-related outcomes is less well known. Our objectives were to identify adherence rates of ICT, and to assess methods of measurement, predictors of adherence, and adherence-related health outcomes in the literature published between 1980 and 2020. Of 543 articles, 43 met the inclusion criteria. Studies measured ICT adherence, predictors, and/or outcomes associated with adherence. Most studies were across multiple countries in Europe and North America (n = 8/43, 18.6%), recruited in clinics (n = 39/43, 90.7%), and focused on β-thalassemia (β-thal) (n = 25/43, 58.1%). Common methods of assessing ICT adherence included patient self-report (n = 24/43, 55.8%), pill count (n = 9/43, 20.9%), prescription refill history (n = 3/43, 7.0%), provider scoring (n = 3/43, 7.0%), and combinations of methods (n = 4/43, 9.3%). Studies reported adherence either in 'categories' with different levels of adherence (n = 24) or 'quantitatively' as a percentage of doses of medication taken out of those prescribed (n = 17). Adherence levels varied (median 91.7%, range 42.0-99.97%). Studies varied in sample size and methods of adherence assessment and reporting, which prohibited meta-analysis. Due to a lack of consensus on how adherence is defined, it is difficult to compare ICT adherence reporting. Further research is needed to establish guidelines for assessing adherence and identifying suboptimal adherence. Behavioral digital interventions have the potential to optimize ICT adherence and health outcomes.
{"title":"Adherence to Iron Chelation Therapy among Adults with Thalassemia: A Systematic Review.","authors":"Margaret Locke, Paavani S Reddy, Sherif M Badawy","doi":"10.1080/03630269.2022.2072320","DOIUrl":"https://doi.org/10.1080/03630269.2022.2072320","url":null,"abstract":"<p><p>Iron chelation therapy (ICT) is essential to prevent complications of iron overload in patients with transfusion-dependent thalassemia. However, the role that adherence to ICT plays in health-related outcomes is less well known. Our objectives were to identify adherence rates of ICT, and to assess methods of measurement, predictors of adherence, and adherence-related health outcomes in the literature published between 1980 and 2020. Of 543 articles, 43 met the inclusion criteria. Studies measured ICT adherence, predictors, and/or outcomes associated with adherence. Most studies were across multiple countries in Europe and North America (<i>n</i> = 8/43, 18.6%), recruited in clinics (<i>n</i> = 39/43, 90.7%), and focused on β-thalassemia (β-thal) (<i>n</i> = 25/43, 58.1%). Common methods of assessing ICT adherence included patient self-report (<i>n</i> = 24/43, 55.8%), pill count (<i>n</i> = 9/43, 20.9%), prescription refill history (<i>n</i> = 3/43, 7.0%), provider scoring (<i>n</i> = 3/43, 7.0%), and combinations of methods (<i>n</i> = 4/43, 9.3%). Studies reported adherence either in 'categories' with different levels of adherence (<i>n</i> = 24) or 'quantitatively' as a percentage of doses of medication taken out of those prescribed (<i>n</i> = 17). Adherence levels varied (median 91.7%, range 42.0-99.97%). Studies varied in sample size and methods of adherence assessment and reporting, which prohibited meta-analysis. Due to a lack of consensus on how adherence is defined, it is difficult to compare ICT adherence reporting. Further research is needed to establish guidelines for assessing adherence and identifying suboptimal adherence. Behavioral digital interventions have the potential to optimize ICT adherence and health outcomes.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9948767/pdf/nihms-1871956.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9940602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-07-01Epub Date: 2022-10-09DOI: 10.1080/03630269.2022.2118604
Xiu-Qin Bao, Ji-Cheng Wang, Dan-Qing Qin, Cui-Ze Yao, Jie Liang, Li Du
β-Thalassemia (β-thal), a highly prevalent disease in tropical and subtropical regions of Southern China, is caused mainly by point mutations in the β-globin gene cluster. However, large deletions have also been found to contribute to some types of β-thal. We identified a novel 5 kb deletion in the β-globin cluster in a Chinese patient using multiplex ligation-dependent probe amplification (MLPA), and characterized it with single molecule real-time (SMRT) sequencing, gap-polymerase chain reaction (gap-PCR) and Sanger sequencing. The deletion was located between positions 5226189 and 5231091 on chromosome 11 (GRCh38), extending from 4 kb upstream of the 5' untranslated region (5'UTR) to the second intron of the β-globin gene. The patient with this deletion presented with microcytosis and hypochromic red cells, as well as relatively high Hb F and Hb A2 levels. Our research indicated that SMRT sequencing is a useful tool for accurate detection of large deletions. Our study broadens the spectrum of deletional β-thalassemias and provides a perspective for further study of the function of the β-globin cluster.
{"title":"A Novel 5 kb Deletion in the <b>β</b>-Globin Gene Cluster Identified in a Chinese Patient.","authors":"Xiu-Qin Bao, Ji-Cheng Wang, Dan-Qing Qin, Cui-Ze Yao, Jie Liang, Li Du","doi":"10.1080/03630269.2022.2118604","DOIUrl":"https://doi.org/10.1080/03630269.2022.2118604","url":null,"abstract":"<p><p>β-Thalassemia (β-thal), a highly prevalent disease in tropical and subtropical regions of Southern China, is caused mainly by point mutations in the β-globin gene cluster. However, large deletions have also been found to contribute to some types of β-thal. We identified a novel 5 kb deletion in the β-globin cluster in a Chinese patient using multiplex ligation-dependent probe amplification (MLPA), and characterized it with single molecule real-time (SMRT) sequencing, gap-polymerase chain reaction (gap-PCR) and Sanger sequencing. The deletion was located between positions 5226189 and 5231091 on chromosome 11 (GRCh38), extending from 4 kb upstream of the 5' untranslated region (5'UTR) to the second intron of the β-globin gene. The patient with this deletion presented with microcytosis and hypochromic red cells, as well as relatively high Hb F and Hb A<sub>2</sub> levels. Our research indicated that SMRT sequencing is a useful tool for accurate detection of large deletions. Our study broadens the spectrum of deletional β-thalassemias and provides a perspective for further study of the function of the β-globin cluster.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33496227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-07-01Epub Date: 2022-09-08DOI: 10.1080/03630269.2022.2118603
Prashant P Warang, Nikhil S Shinde, Vinod D Umare, Prajyot V Deshmukh, Kanjaksha Ghosh, Manisha R Madkaikar, Roshan B Colah, Malay B Mukherjee
Fermented papaya preparation (FPP) is the source of antioxidants that may help in reducing the complications associated with oxidative stress and may improve the quality of life in sickle cell disease patients. In this study, we assessed the in vitro effect of FPP on sickled red blood cells (RBCs) using oxidative stress markers and observed that FPP has the potential to reduce the oxidative stress. Scanning electron microscopy (SEM) and eosin 5' malaemide (E5'M) dye test showed that FPP protects red cell morphology against the oxidative stress. Liquid chromatography mass spectrometry (LCMS) analysis of FPP suggests the presence of essential amino acids, vitamin D3, and its derivatives. Fermented papaya preparation can be of benefit either in reducing oxidative stress parameters or in preventing pathophysiological events in the sickle cell disease patients.
{"title":"Role of Oxidative Stress and the Protective Effect of Fermented Papaya Preparation in Sickle Cell Disease.","authors":"Prashant P Warang, Nikhil S Shinde, Vinod D Umare, Prajyot V Deshmukh, Kanjaksha Ghosh, Manisha R Madkaikar, Roshan B Colah, Malay B Mukherjee","doi":"10.1080/03630269.2022.2118603","DOIUrl":"https://doi.org/10.1080/03630269.2022.2118603","url":null,"abstract":"<p><p>Fermented papaya preparation (FPP) is the source of antioxidants that may help in reducing the complications associated with oxidative stress and may improve the quality of life in sickle cell disease patients. In this study, we assessed the <i>in vitro</i> effect of FPP on sickled red blood cells (RBCs) using oxidative stress markers and observed that FPP has the potential to reduce the oxidative stress. Scanning electron microscopy (SEM) and eosin 5' malaemide (E5'M) dye test showed that FPP protects red cell morphology against the oxidative stress. Liquid chromatography mass spectrometry (LCMS) analysis of FPP suggests the presence of essential amino acids, vitamin D3, and its derivatives. Fermented papaya preparation can be of benefit either in reducing oxidative stress parameters or in preventing pathophysiological events in the sickle cell disease patients.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33449407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}